What is the difference between cefadroxyl (Cefadroxil) and cefixime (Cefixime) in terms of spectrum of activity and usage?

Cefadroxil vs Cefixime: Spectrum and Clinical Usage

Cefadroxil is a first-generation cephalosporin with primarily gram-positive coverage and limited gram-negative activity, while cefixime is a third-generation cephalosporin with potent gram-negative activity but limited gram-positive coverage—they occupy fundamentally different therapeutic niches and are not interchangeable.

Spectrum of Activity

Cefadroxil (First-Generation)

• Gram-positive coverage: Good activity against Streptococcus pyogenes, Streptococcus pneumoniae (penicillin-susceptible strains), and methicillin-susceptible Staphylococcus aureus 1
• Gram-negative coverage: Limited to basic organisms; poor activity against Haemophilus influenzae and most Enterobacteriaceae 1
• Anaerobic coverage: Minimal to none 1
• Beta-lactamase stability: Poor—easily hydrolyzed by beta-lactamases 1

Cefixime (Third-Generation)

• Gram-negative coverage: Potent activity against H. influenzae (including beta-lactamase-producing strains), Neisseria gonorrhoeae, and most Enterobacteriaceae 1, 2
• Gram-positive coverage: Limited activity against S. pneumoniae (penicillin-susceptible only); no activity against staphylococci; may fail against even penicillin-susceptible pneumococci 1
• Drug-resistant S. pneumoniae (DRSP): No clinically significant activity 1
• Pseudomonas aeruginosa: Inactive 2
• Beta-lactamase stability: Resistant to hydrolysis by many beta-lactamases 2, 3

Clinical Usage Patterns

Cefadroxil Indications

• Skin and soft tissue infections caused by streptococci or staphylococci (community-acquired, non-MRSA) 1
• Pharyngitis/tonsillitis due to S. pyogenes 1
• Simple urinary tract infections in areas with low E. coli resistance 1
• Dosing advantage: Typically once or twice daily due to longer half-life among first-generation agents 1

Cefixime Indications

• Acute otitis media: Effective against H. influenzae and S. pneumoniae at 8 mg/kg daily 2
• Acute bacterial rhinosinusitis: When H. influenzae is suspected, though limited pneumococcal coverage is a concern 1
• Uncomplicated gonorrhea: Single-dose therapy for penicillinase-producing N. gonorrhoeae 2, 3
• Uncomplicated urinary tract infections: Alternative to amoxicillin or co-trimoxazole 2, 3
• Lower respiratory tract infections: When gram-negative pathogens predominate, though inadequate for empiric pneumonia due to poor pneumococcal coverage 2
• Dosing advantage: 3-hour elimination half-life permits once or twice daily administration 2, 3

Critical Clinical Distinctions

When Cefadroxil Fails

Cefadroxil is inappropriate for:

• Infections involving H. influenzae (respiratory tract infections, otitis media) 1
• Beta-lactamase-producing organisms 1
• Gram-negative urinary tract infections in areas with high resistance 1
• Any infection requiring gram-negative coverage 1

When Cefixime Fails

Cefixime is inappropriate for:

• Empiric community-acquired pneumonia (inadequate S. pneumoniae coverage, especially DRSP) 1
• Staphylococcal infections (skin/soft tissue, bacteremia) 1, 2
• Pseudomonas aeruginosa infections 2
• Anaerobic infections (Bacteroides fragilis) 1
• Enterococcal infections 1

Practical Algorithm for Selection

Choose Cefadroxil when:

1. Confirmed or highly suspected gram-positive infection (streptococcal pharyngitis, simple cellulitis)
2. No concern for beta-lactamase-producing organisms
3. No gram-negative pathogen involvement expected

Choose Cefixime when:

1. H. influenzae is confirmed or suspected (otitis media, sinusitis)
2. Uncomplicated gonorrhea
3. Gram-negative urinary tract infection
4. BUT always ensure adequate gram-positive coverage is not needed first

Never substitute one for the other as they address opposite ends of the bacterial spectrum—cefadroxil targets gram-positives while cefixime targets gram-negatives 1, 2.

Adverse Effects

Both agents share similar cephalosporin class adverse effects, with diarrhea and stool changes being most common (up to 20% with cefixime), typically mild to moderate and transient 2, 3.